Prevalence of cardiovascular disease in type 2 diabetes: a systematic literature review of scientific evidence from across the world in 2007-2017.

BACKGROUND: Cardiovascular disease (CVD) is a common comorbidity in type 2 diabetes (T2DM). CVD's prevalence has been growing over time. PURPOSE: To estimate the current prevalence of CVD among adults with T2DM by reviewing literature published within the last 10 years (2007-March 2017). METHODS: We searched Medline, Embase, and proceedings of major scientific meetings for original research documenting the prevalence of CVD in T2DM. CVD included stroke, myocardial infarction, angina pectoris, heart failure, ischemic heart disease, cardiovascular disease, coronary heart disease, atherosclerosis, and cardiovascular death. No restrictions were placed on country of origin or publication language. Two reviewers independently searched for articles and extracted data, adjudicating results through consensus. Data were summarized descriptively. Risk of bias was examined by applying the STROBE checklist. RESULTS: We analyzed data from 57 articles with 4,549,481 persons having T2DM. Europe produced the most articles (46%), followed by the Western Pacific/China (21%), and North America (13%). Overall in 4,549,481 persons with T2DM, 52.0% were male, 47.0% were obese, aged 63.6 ± 6.9 years old, with T2DM duration of 10.4 ± 3.7 years. CVD affected 32.2% overall (53 studies, N = 4,289,140); 29.1% had atherosclerosis (4 studies, N = 1153), 21.2% had coronary heart disease (42 articles, N = 3,833,200), 14.9% heart failure (14 studies, N = 601,154), 14.6% angina (4 studies, N = 354,743), 10.0% myocardial infarction (13 studies, N = 3,518,833) and 7.6% stroke (39 studies, N = 3,901,505). CVD was the cause of death in 9.9% of T2DM patients (representing 50.3% of all deaths). Risk of bias was low; 80 ± 12% of STROBE checklist items were adequately addressed. CONCLUSIONS: Globally, overall CVD affects approximately 32.2% of all persons with T2DM. CVD is a major cause of mortality among people with T2DM, accounting for approximately half of all deaths over the study period. Coronary artery disease and stroke were the major contributors.

Economic Burden of Cardiovascular Disease in Type 2 Diabetes: A Systematic Review.

BACKGROUND: Cardiovascular diseases (CVDs) constitute major comorbidities in type 2 diabetes mellitus (T2DM), contributing substantially to treatment costs for T2DM. An updated overview of the economic burden of CVD in T2DM has not been presented to date. OBJECTIVE: To systematically review published articles describing the costs associated with treating CVD in people with T2DM. METHODS: Two reviewers searched MEDLINE, Embase, and abstracts from scientific meetings to identify original research published between 2007 and 2017, with no restrictions on language. Studies reporting direct costs at either a macro level (e.g., burden of illness for a country) or a micro level (e.g., cost incurred by one patient) were included. Extracted costs were inflated to 2016 values using local consumer price indexes, converted into US dollars, and presented as cost per patient per year. RESULTS: Of 81 identified articles, 24 were accepted for analysis, of which 14 were full articles and 10 abstracts. Cardiovascular comorbidities in patients with T2DM incurred a significant burden at both the population and patient levels. From a population level, CVD costs contributed between 20% and 49% of the total direct costs of treating T2DM. The median annual costs per patient for CVD, coronary artery disease, heart failure, and stroke were, respectively, 112%, 107%, 59%, and 322% higher compared with those for T2DM patients without CVD. On average, treating patients with CVD and T2DM resulted in a cost increase ranging from $3418 to $9705 compared with treating patients with T2DM alone. CONCLUSIONS: Globally, CVD has a substantial impact on direct medical costs of T2DM at both the patient and population levels.

Pharmacoeconomics of depot antipsychotics for treating chronic schizophrenia in Sweden.

AIMS: To determine the cost-effectiveness of long-acting injectable (LAI) antipsychotics for chronic schizophrenia in Sweden. METHODS: A 1-year decision tree was developed for Sweden using published data and expert opinion. Five treatment strategies lasting 1 year were compared: paliperidone palmitate (PP-LAI), olanzapine pamoate (OLZ-LAI), risperidone (RIS-LAI), haloperidol decanoate (HAL-LAI) and olanzapine tablets (oral-OLZ). Patients intolerant/failing drugs switched to another depot; subsequent failures received clozapine. Resources and employment time lost (indirect costs) were costed in 2011 Swedish kroner (SEK), from standard government lists. The model calculated the average cost/patient and quality-adjusted life-years (QALYs), which were combined into incremental cost-effectiveness ratios. Multivariate and 1-way sensitivity analyses tested model stability. RESULTS: PP-LAI followed by OLZ-LAI had the lowest cost/patient (189,696 SEK) and highest QALYs (0.817), dominating in the base case. OLZ-LAI followed by PP-LAI cost 229,775 SEK (0.812 QALY), RIS-LAI followed by HAL-LAI cost 221,062 SEK (0.804 QALY), HAL-LAI followed by oral-OLZ cost 243,411 SEK (0.776 QALY), and oral-OLZ followed by HAL-LAI cost 249,422 SEK (0.773 QALY). The greatest proportions of costs (52.5-83.8%) were for institutional care; indirect costs were minor (2.4-3.8%). RESULTS were sensitive to adherence and hospitalization rates, but not drug cost. PP-LAI followed by OLZ-LAI dominated OLZ-LAI followed by PP-LAI in 59.4% of simulations, RIS-LAI followed by HAL-LAI in 65.8%, HAL-LAI followed by oral-OLZ in 94.0% and oral-OLZ followed by HAL-LAI in 95.9%; PP-LAI followed by OLZ-LAI was dominated in 1.1% of the 40,000 iterations. CONCLUSION: PP-LAI followed by OLZ-LAI was cost-effective in Sweden for chronic schizophrenia and cost-saving overall to the healthcare system.

Pharmacoeconomic analysis of paliperidone palmitate versus olanzapine pamoate for chronic schizophrenia in Norway.

OBJECTIVE: Paliperidone palmitate long-acting injection (PP-LAI) has recently been approved for treatment of chronic schizophrenia. Its cost-effectiveness has not been established. The objective was to compare direct costs and outcomes between PP-LAI and olanzapine pamoate (OLZ-LAI) in treating chronic schizophrenia in Norway from the perspective of the government payer. METHODS: We used a decision analytic model over a 1-year time horizon. Clinical inputs were derived from the literature and an expert panel; costs were taken from standard lists, adjusted to 2010 Norwegian kroner (NOK). Discounting was not done. Main outcomes included average cost per patient treated, hospitalisations, emergency room (ER) visits and quality-adjusted life years (QALYs). The pharmacoeconomic outcome was the incremental cost per QALY. Robustness was examined using one-way sensitivity analyses on critical variables and a 5000-iteration probabilistic Monte Carlo sensitivity analysis with all variables included. RESULTS: PP-LAI generated 0.845 QALY at a cost of 151 336 NOK of which 23% was due to drugs; 25% of patients were hospitalised and another 12% required ER visits. OLZ-LAI cost 174 351 NOK (21% due to drugs); patient outcomes included 0.844 QALY, 27% hospitalisations and 14% ER visits. PP-LAI dominated OLZ-LAI in the base case. The analysis was reasonably robust against variations in drug cost but sensitive to small changes in adherence and hospitalisation rates. Overall, PP-LAI was dominant over OLZ-LAI in 54.5% of simulations. Replacing OLZ-LAI with PP-LAI would be cost saving for the Norwegian healthcare system. CONCLUSION: PP-LAI was cost-effective compared with OLZ-LAI in treating patients with chronic schizophrenia in Norway but sensitive to changes in adherence and hospitalisation rates.

An analysis of potentially prolactin-related adverse events and abnormal prolactin values in randomized clinical trials with paliperidone palmitate.

BACKGROUND: Paliperidone palmitate has been associated with serum prolactin elevations in some patients. However, few individuals with elevated prolactin levels (hyperprolactinemia) have symptomatic potentially prolactin-related adverse events (PPR-AEs). OBJECTIVE: To quantify rates of hyperprolactinemia in subjects treated with the newly marketed paliperidone palmitate long-acting injection (PP-LAI) in randomized clinical trials, summarize rates of PPR-AEs in those trials by sex and dose, and determine how many PPR-AEs required treatment. METHODS: Numbers and rates of investigator-reported hyperprolactinemia and PPR-AEs were obtained from the sponsor's clinical trial database and have been included in regulatory filings. Results were tabulated for males, females, and overall, and by dose administered, using descriptive statistics. Those requiring treatment were described as well. RESULTS: There were 3173 subjects (61.4% males) exposed to PP-LAI in 10 clinical trials; 2831 (89.2%) patients had recorded prolactin levels, including 1759 males (90.3% of exposed males) and 1072 females (87.5% of exposed females). Overall, at any time, prolactin levels were elevated for 38.8% of the subjects (39.5% for males and 37.7% for females; p = 0.354 between sexes). However, there was no significant correlation between monthly dose and proportion of subjects with elevated prolactin levels (p = 0.109). There were 115 PPR-AEs in 107 patients (3.4%); 51 (44.3% of PPR-AEs) cases represented asymptomatic hyperprolactinemia. The remaining 64 symptomatic PPR-AEs affected 2.0% of the total number of subjects. Fifteen events in 13 participants (0.41% of patients or 4.7 events/1000 patients) required treatment. CONCLUSIONS: Clinicians should periodically assess patients on paliperidone palmitate for any PPR-AEs and carefully assess the benefits and risks when managing these effects.

Health state utilities and quality of life in patients with hepatitis B.

BACKGROUND: The effect of chronic hepatitis B (CHB) infection on health-related quality of life (HRQoL) and health state utilities has not been well characterized. OBJECTIVE: To measure utility scores and HRQoL across disease states associated with CHB infection. METHODS: Patients attending four tertiary care clinics for CHB were approached between July 2007 and March 2009. Respondents completed version 2 of the Short-Form 36 Health Survey, the EQ5D, a visual analogue scale, the Health Utilities Index Mark 3, standard gamble, and demographics and risk factor surveys in English, Cantonese or Mandarin. Charts were reviewed to determine disease stage and comorbidities. RESULTS: A total of 433 patients were studied: 294 had no cirrhosis; 79 had compensated cirrhosis; seven had decompensated cirrhosis; 23 had hepatocellular carcinoma; and 30 had received a liver transplant. The mean standard gamble utilities for these disease states were 0.89, 0.87, 0.82, 0.84 and 0.86, respectively. HRQoL scores in noncirrhotic patients were similar to those of the general population. Scores of patients with compensated cirrhosis were not significantly lower; however, patients with decompensated cirrhosis and hepatocellular carcinoma had significantly lower HRQoL scores compared with noncirrhotic patients (P<0.05). Similar scores were observed among patients on and off oral antiviral treatment. Post-liver transplant patients had a higher HRQoL than patients with decompensated cirrhosis. Age, number of comorbidities and relationship status were significantly associated with HRQoL scores. CONCLUSIONS: HRQoL in CHB patients is only impaired in the later stages of liver disease. Neither CHB infection nor antiviral treatment is associated with a lower quality of life.

Pharmacoeconomic analysis of paliperidone palmitate for treating schizophrenia in Greece.

BACKGROUND: Patients having chronic schizophrenia with frequent relapses and hospitalizations represent a great challenge, both clinically and financially. Risperidone long-acting injection (RIS-LAI) has been the main LAI atypical antipsychotic treatment in Greece. Paliperidone palmitate (PP-LAI) has recently been approved. It is dosed monthly, as opposed to biweekly for RIS-LAI, but such advantages have not yet been analysed in terms of economic evaluation. PURPOSE: To compare costs and outcomes of PP-LAI versus RIS-LAI in Greece. METHODS: A cost-utility analysis was performed using a previously validated decision tree to model clinical pathways and costs over 1 year for stable patients started on either medication. Rates were taken from the literature. A local expert panel provided feedback on treatment patterns. All direct costs incurred by the national healthcare system were obtained from the literature and standard price lists; all were inflated to 2011 costs. Patient outcomes analyzed included average days with stable disease, numbers of hospitalizations, emergency room visits, and quality-adjusted life-years (QALYs). RESULTS: The total annual healthcare cost with PP-LAI was €3529; patients experienced 325 days in remission and 0.840 QALY; 28% were hospitalized and 15% received emergency room treatment. With RIS-LAI, the cost was €3695, patients experienced 318.6 days in remission and 0.815 QALY; 33% were hospitalized and 17% received emergency room treatment. Thus, PP-LAI dominated RIS-LAI. Results were generally robust in sensitivity analyses with PP-LAI dominating in 74.6% of simulations. Results were sensitive to the price of PP-LAI. CONCLUSIONS: PP-LAI appears to be a cost-effective option for treating chronic schizophrenia in Greece compared with RIS-LAI since it results in savings to the health care system along with better patient outcomes.

Tenofovir and entecavir are the most effective antiviral agents for chronic hepatitis B: a systematic review and Bayesian meta-analyses.

BACKGROUND & AIMS: The relative efficacies of licensed antiviral therapies for treatment-naive chronic hepatitis B (CHB) infection in randomized controlled trials have not been determined. We evaluated the relative efficacies of the first 12 months of CHB treatments. METHODS: Drugs evaluated were lamivudine, pegylated interferon, adefovir, entecavir, telbivudine, and tenofovir, as monotherapies and combination therapies, in treatment-naive individuals. Databases were searched for randomized controlled trials of the first 12 months of therapy in hepatitis B e antigen (HBeAg)-positive and/or HBeAg-negative patients with CHB published in English before October 31, 2009. Bayesian mixed treatment comparisons were used to calculate the odds ratios, including 95% credible intervals and predicted probabilities of surrogate outcomes to determine the relative effects of each treatment. RESULTS: In HBeAg-positive patients, tenofovir was most effective in inducing undetectable levels of HBV DNA (predicted probability, 88%), normalization of alanine aminotransferase (ALT) levels (66%), HBeAg seroconversion (20%), and hepatitis B surface antigen loss (5%); it ranked third in histologic improvement of the liver (53%). Entecavir was most effective in improving liver histology (56%), second for inducing undetectable levels of HBV DNA (61%) and normalization of ALT levels (70%), and third in loss of hepatitis B surface antigen (1%). In HBeAg-negative patients, tenofovir was the most effective in inducing undetectable levels of HBV DNA (94%) and improving liver histology (65%); it ranked second for normalization of ALT levels (73%). CONCLUSIONS: In the first year of treatment for CHB, tenofovir and entecavir are the most potent oral antiviral agents for HBeAg-positive patients; tenofovir is most effective for HBeAg-negative patients.

Out-of-pocket expenditures and coping strategies for people living with HIV: Bogotá, Colombia, 2009.

Our objective was to estimate the out-of-pocket expenditure related to medical and non-medical items on health care covered by individuals or household members, and to describe coping strategies they use to meet the financial burden. We undertook a cross-sectional survey with a convenience sample of 540 adults with HIV living in urban areas of Bogotá, Colombia. Univariate and bivariate analyses were done. We found that although 95% of the patients with HIV in the sample had health insurance, individuals and families spent about 13% of their incomes on medical and non-medical items monthly. Those costs increased for patients taking the second or third antiretroviral drug (ARV) treatment scheme and for patients with AIDS-related physical disabilities. We found statistically significant differences in spending among different insurance plans and socioeconomic status (SES; p≤0.05). As a result of the high out-of-pocket expenses, households had to alter their budgets, reducing consumption of basic needs and modifying financial and social family dynamics. Those coping strategies might increase both current and structural poverty. Lack of comprehensive health care increases the economic burden for patients, in terms of financial but also social impact.

Systematic review and meta-analysis of the effect of warming local anesthetics on injection pain.

STUDY OBJECTIVE: Local anesthetics are the main class of analgesics used for pain management during laceration repair and other minor surgeries; however, they are administered by injection, which is painful. Warming local anesthetics has been proposed as a cost-free intervention that reduces injection pain. A systematic review of the effectiveness of this technique has not yet been undertaken. We determine the effectiveness of warming local anesthetics to reduce pain in adults and children undergoing local anesthetic infiltration into intradermal or subcutaneous tissue. METHODS: We used published articles from MEDLINE (1950 to June 2010), EMBASE (1980 to June 2010), CINAHL (1982 to June 2010), the Cochrane Library (second quarter 2010), International Pharmaceutical Abstracts (1970 to June 2010), and ProQuest Dissertations and Theses database (1938 to June 2010). We included studies with randomized or pseudorandomized designs and healthy subjects or patients receiving subcutaneous or intradermal injection of local anesthetics that were warmed (body temperature) or not (room temperature). Studies of regional anesthesia and intraarticular, spinal, or periorbital administration of local anesthetics were excluded. Data were extracted onto predesigned forms and verified by 2 reviewers. Quality was assessed with the Cochrane risk of bias tool. The primary outcome was self-reported pain as assessed by a visual analog or numeric rating scale. Data were combined with mean differences with 95% confidence intervals (CIs) by using a random-effects model. RESULTS: Twenty-nine studies were retrieved for close examination and 19 studies met inclusion criteria. A total of 18 studies with 831 patients could be included in a meta-analysis. Seventeen studies had an unclear risk of bias and 1 had a high risk of bias. A mean difference of -11 mm (95% CI -14 to -7 mm) on a 100-mm scale was found in favor of warming local anesthetics. Subgroup analysis of 8 studies investigating the effect of warming on buffered local anesthetics yielded similar results: -7 mm (95% CI -12 to -3 mm). CONCLUSION: Warming local anesthetics leads to less pain during injection and therefore should be done before administration.

Medication utilization and illness management study in Nigeria.

BACKGROUND: Little is known about rates of illness, illness management, or drug utilization in developing countries. OBJECTIVE: To determine patterns of illness and drug utilization in urban and rural households in Nigeria. METHODS: A survey was developed and validated for data collection. A random sample from some communities in Owan East Local Government Area (LGA) of Edo State, Nigeria, was selected, based on a national population survey, using both the supervisory and enumeration areas of the LGA. We determined the sample size using methods described by Cochran, including 5% precision, 5% α, and allowing for 5% data error. Respondents were queried in face-to-face interviews about illnesses in their households during the previous 2 weeks; demographic information; how they were treated; and where they sought treatment, advice, and medicines. As well, we determined how they kept families well. Descriptive statistics were used to summarize data. RESULTS: Out of 549 persons, 497 completed the questionnaires, giving a response rate of 90.5%. Of these respondents, 395 (79.5%) reported 517 illnesses during the previous 2 weeks. The average age of the ill person was 30.6 ± 24.3 years (range 3 months to 95 years). Percentages by age were: infants younger than 1 year 1.0%, children aged 1-17 years 36.0%, and adults aged ≥18 years 63.0%. Average monthly income per household was low (13,247 naira/88.31 US$). Malaria and its symptoms (fever, chills, joint pain, headache, gastrointestinal problems) and upper respiratory symptoms were most common. A majority (44.8%) of the ill persons self-treated, with 93.6% using antibiotic and antimalarial drugs. Among the households surveyed, 42.1% had drugs on hand (average 2.3 ± 1.3, range 1-7, median 2) for disease prevention, and the most used drugs were analgesics (46.2%) and antimalarial drugs (37.3%). CONCLUSIONS: Illness is frequent in Nigeria and is usually self-treated with antibiotic and antimalarial drugs. Medications were reported to be the most frequently used measure to prevent household illness. The implications of these findings are discussed.

Nausea and vomiting of pregnancy (NVP) and depression: cause or effect?

BACKGROUND: Both nausea and vomiting and depression are common conditions affecting women during pregnancy. Several studies have linked depression with nausea and vomiting of pregnancy (NVP); however, researchers were unable to determine whether depression was caused by NVP or by a pre-existing condition. OBJECTIVE: To determine whether NVP is associated with depression in women with no history of depression prior to pregnancy. STUDY DESIGN AND METHODS: This was a prospective, observational, longitudinal study. Women with no diagnosis of depression who contacted The Motherisk Program prior to becoming pregnant or were at < 6 weeks gestation were enrolled in the study. Each woman was interviewed at 8, 11, 18, 30 weeks gestation and at 6-18 weeks post-partum. At each interview, we administered the EDPS, Wellbeing and PUQE questionnaires and analyzed the data for correlation between depression and NVP. RESULTS: Data were analyzed obtained from 57 women. There were five EPDS scores ≥13 (one at baseline and two each at weeks 8 and 11) considered indicative of depression and 11 cases with PUQE scores ≥7, indicative of moderate-high severity of NVP. We did not find an association between high PUQE scores and high EPDS scores and conversely, there was no relationship between high EPDS scores and high PUQE scores. CONCLUSION: No association between depressive symptoms and NVP was observed; however, our sample size was very small and further studies could be done with a larger population of pregnant women.

International drug price comparisons: quality assessment.

OBJECTIVE: To quantitatively summarize results (i.e., prices and affordability) reported from international drug price comparison studies and assess their methodological quality. METHODS: A systematic search of the most relevant databases-Medline, Embase, International Pharmaceutical Abstracts (IPA), and Scopus, from their inception to May 2009-was conducted to identify original research comparing international drug prices. International drug price information was extracted and recorded from accepted papers. Affordability was reported as drug prices adjusted for income. Study quality was assessed using six criteria: use of similar countries, use of a representative sample of drugs, selection of specific types of prices, identification of drug packaging, different weights on price indices, and the type of currency conversion used. RESULTS: Of the 1 828 studies identified, 21 were included. Only one study adequately addressed all quality issues. A large variation in study quality was observed due to the many methods used to conduct the drug price comparisons, such as different indices, economic parameters, price types, basket of drugs, and more. Thus, the quality of published studies was considered poor. Results varied across studies, but generally, higher income countries had higher drug prices. However, after adjusting drug prices for affordability, higher income countries had more affordable prices than lower income countries. CONCLUSIONS: Differences between drug prices and affordability in different countries were found. Low income countries reported less affordability of drugs, leaving room for potential problems with drug access, and consequently, a negative impact on health. The quality of the literature on this topic needs improvement.

Relationship between blood glucose and carotid intima media thickness: A meta-analysis.

BACKGROUND: Increased coronary intima media thickness (CIMT) has been associated with adverse cardiovascular outcomes, as have increased glucose levels. The link has not been established between glucose and CIMT; therefore, we sought to assess the relationship between glucose and CIMT. METHODS: Medline, EMBASE, Scopus, and Cochrane databases were searched from inception through 2009 for original research reporting both postprandial glucose levels and CIMT measurements. Glucose was classified as normal, impaired, or diabetic. Outputs included inverse variance weighted effect size and also average correlation (using the Wang and Bushman approach). Data were combined using a random effects meta-analytic model. Heterogeneity as assessed using chi(2) and I(2); bias was examined using Egger plots and Begg-Mazumdar tau. Polynomial functions (i.e., linear, quadratic, cubic, quartic) were fit to the data and the Akaike Information Criteria were used to select the optimal model. RESULTS: We identified 172 papers; 161 were rejected (19 inappropriate design, 8 had selected patients, 101 inappropriate outcomes) leaving 11 accepted. We used data from 15,592 patients (8250 normals, 3013 impaired glucose, 4329 diabetics). There was no evidence of heterogeneity or publication bias. The overall correlation was 0.082 (CI95%:0.066-0.098); the overall effect size was 0.294 (0.245-0.343) between diabetics and normals and 0.137 (0.072-0.202) between normals and those with impaired glucose. The equation of best fit was linear (CIMT = 0.828 + 0.009*glucose). CONCLUSIONS: There is a small but significant relationship between postprandial glucose levels and CIMT, which have both been associated with adverse cardiovascular outcomes.

Cost-benefit analysis of pharmacist interventions over 36 months in a university hospital.

OBJECTIVE: To perform a cost-benefits analysis of a clinical pharmacy (CP) service implemented in a Neurology ward of a tertiary teaching hospital. METHODS: This is a cost-benefit analysis of a single arm, prospective cohort study performed at the adult Neurology Unit over 36 months, which has evaluated the results of a CP service from a hospital and Public Health System (PHS) perspective. The interventions were classified into 14 categories and the costs identified as direct medical costs. The results were analyzed by the total and marginal cost, the benefit-cost ratio (BCR) and the net benefit (NB). RESULTS: The total 334 patients were followed-up and the highest occurrence in 506 interventions was drug introduction (29.0%). The marginal cost for the hospital and avoided cost for PHS was US$182±32 and US$25,536±4,923 per year; and US$0.55 and US$76.4 per patient/year. The BCR and NB were 0.0, -US$26,105 (95%CI -31,850 - -10,610), -US$27,112 (95%CI -33,160-11,720) for the hospital and; 3.0 (95%CI 1.97-4.94), US$51,048 (95%CI 27,645-75,716) and, 4.6 (95%CI 2.24-10.05), US$91,496 (95%CI 34,700-168,050; p < 0.001) for the PHS, both considering adhered and total interventions, respectively. CONCLUSIONS: The CP service was not directly cost-benefit at the hospital perspective, but it presented savings for forecast cost related to the occurrence of preventable morbidities, measuring a good cost-benefit for the PHS.

The safety of proton pump inhibitors (PPIs) in pregnancy: a meta-analysis.

OBJECTIVES: Heartburn and acid reflux are common medical disorders in pregnancy and can result in serious discomfort and complications. Furthermore, some pregnant women also experience more severe gastrointestinal conditions, such as Helicobacter pylori infections, peptic ulcers, and Zollinger-Ellison syndrome. To allow the use of proton pump inhibitors (PPIs) in pregnancy, the fetal safety of this drug class must be established. The aim of this study is to determine the fetal safety of PPIs during early pregnancy through systematic literature review. METHODS: All original research assessing the safety of PPIs in pregnancy was sought from inception to July 2008. Two independent reviewers identified articles, compared results, and settled differences through consensus. The Downs-Black scale was used to assess quality. Data assessed included congenital malformations, spontaneous abortions, and preterm delivery. A random effects meta-analysis combined the results from included studies. RESULTS: Of the 60 articles identified, 7 met our inclusion criteria. Using data from 134,940 patients, including 1,530 exposed and 133,410 not exposed to PPIs, the overall odds ratio (OR) for major malformations was 1.12 (95% confidence interval, CI: 0.86-1.45). Further analysis revealed no increased risk for spontaneous abortions (OR=1.29, 95% CI: 0.84-1.97); similarly, there was no increased risk for preterm delivery (OR=1.13, 95% CI: 0.96-1.33). In the secondary analysis of 1,341 exposed and 120,137 not exposed to omeprazole alone, the OR and 95% CI for major malformations were 1.17 and 0.90-1.53, respectively. CONCLUSIONS: On the basis of these results, PPIs are not associated with an increased risk for major congenital birth defects, spontaneous abortions, or preterm delivery. The narrow range of 95% CIs is further reassuring, suggesting that PPIs can be safely used in pregnancy.

Willingness to pay for a treatment for pain in multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a chronic neurological disease that affects 240 per 100 000 Canadians. Of these patients, 10-80% (average 70%) experience pain. Sativex is a cannabis-based drug recently approved for neuropathic pain. OBJECTIVES: In this study, we determine individuals' preferences between two treatment options as well as the willingness to pay (WTP) for Sativex, expressed as the amount they would pay in insurance premiums to have access to that treatment. METHODS: The WTP instrument comprised a decision board as a visual aid, and a questionnaire. A decision board helps clinicians standardize the presentation of treatment information. In this study, the decision board described two treatment options: a three-drug combination (gabapentin, amytriptyline, acetaminophen [paracetamol] {i.e. pills}) and the three-drug combination plus Sativex (i.e. 'pills and oral spray'). Information on efficacy and adverse effects was taken from trial data; wording was guided by a panel of neurologists and tested for clarity on lay people. The instrument was administered to 500 participants from Canada's general population using the bidding game approach. Descriptive statistics were calculated. RESULTS: Mean (SD) age of participants was 39 (13) years, with a female : male distribution of 56 : 44. The decision board was presented in both English (85%) and French (15%). Of 500 interviewees, 253 (50.6%) chose the 'pills and oral spray'. Mean monthly WTP for the insurance premium for those who chose the 'pills and oral spray' was Can dollars 8 (SD +/- 15, median 4, range 0-200). CONCLUSIONS: Assuming that 51% of the general population are willing to pay additional premiums as reported in this study, the premiums collected would cover the cost of Sativex for all Canadian MS patients experiencing pain, with a surplus.

Rates of spontaneous and therapeutic abortions following use of antidepressants in pregnancy: results from a large prospective database.

OBJECTIVE: The use of antidepressants during pregnancy remains a controversial issue, and there is little information on the risk of spontaneous abortions following antidepressant exposure in early pregnancy. We sought to examine whether use of antidepressants increases the rates of spontaneous abortion (SA) and therapeutic abortion (TA) in women exposed in early pregnancy. METHODS: In a cohort of women who contacted the Motherisk program during pregnancy, we compared two groups of women, one exposed and the other not exposed to antidepressants during pregnancy, and calculated the associated rates of SA and TA. RESULTS: Among 937 women exposed to antidepressants prior to and during early pregnancy, there were 122 SAs (13.0%) including three ectopic pregnancies, and in the comparison group there were 75 SAs (8.0%) and no ectopic pregnancies. The relative risk was 1.63 (95% CI 1.24-2.14). Three-fold more women reported a TA in the exposed group, 26 (2.4%) compared to 8 (0.7%) in the non-exposed group (RR 3.25; 95% CI 1.48-7.14). A sub-analysis revealed that in both groups, of 338 women with a prior SA, 58 (17.2%) reported having a SA in the current pregnancy, compared with 61/652 (9.4%) with no prior SA (chi square = 12.09, P lt; 0.001). In the antidepressant group, the incidence was 20.7%, and in the non-exposed group, it was 13.3%. Logistic regression confirmed that only antidepressant exposure and prior SA were significantly associated with current SA. CONCLUSION: Exposure to antidepressants in the first trimester of pregnancy appears to be associated with a small but statistically significant increased risk of SA and decision to terminate a pregnancy. The risk for SA is further elevated with a history of previous SA. However, any underlying depression must be taken into consideration when evaluating these results.

Probiotic safety in pregnancy: a systematic review and meta-analysis of randomized controlled trials of Lactobacillus, Bifidobacterium, and Saccharomyces spp.

Our objective in this study was to review systematically the evidence for safety of Lactobacillus, Bifidobacterium and Saccharomyces spp. during pregnancy and to conduct a meta-analysis of randomized controlled trials (RCTs). Eleven databases were searched from inception to September 2007 for RCTs of probiotic use during pregnancy. Two independent reviewers searched databases. Random-effects models combined data. Eleven studies on Lactobacillus and/or Bifidobacterium examined 1505 patients for four outcomes with no data heterogeneity; no miscarriage data were reported. Five studies reported Caesarean section outcomes (OR 0.88; 95% CI 0.65 to 1.19). Six studies reported birth weight (weighted difference 45 g; 95% CI -181 to 271). Three studies reported gestational age (weighted difference 0.4 weeks; 95%CI -0.4 to 1.2). No malformations were reported in the probiotic group. No RCTs were available for Saccharomyces during pregnancy. Lactobacillus and Bifidobacterium had no effect on the incidence of Caesarean section, birth weight, or gestational age. The safety of Saccharomyces during pregnancy is unknown.

The effectiveness of Proctofoam-HC for treatment of hemorrhoids in late pregnancy.

OBJECTIVE: Currently no topical anti-hemorrhoidal agents have been studied for effectiveness in pregnancy. This study evaluated the effectiveness of Proctofoam-HC used during the last trimester of pregnancy. METHODS: In this prospective, open-label, observational study, pregnant women prescribed Proctofoam-HC were asked to complete two telephone interview questionnaires. RESULTS: A total of 88 women completed the study. All hemorrhoidal symptoms, including pain, pruritus, swelling, itching, decreased significantly (P < 0.001) and overall well-being improved. The improvement was clinically very significant after correction for potential placebo effect. CONCLUSIONS: Proctofoam-HC appears to provide effective treatment of hemorrhoids in late pregnancy.